When refering to evidence in academic writing, you should always try to reference the primary (original) source. That is usually the journal article where the information was first stated. In most cases Physiopedia articles are a secondary source and so should not be used as references. Physiopedia articles are best used to find the original sources of information (see the references list at the bottom of the article).

If you believe that this Physiopedia article is the primary source for the information you are refering to, you can use the button below to access a related citation statement.

Definition/Description

Ehlers-Danlos syndrome is a hereditary collagen disorder characterized by articular hypermobility, dermal hyperelasticity, and widespread tissue fragility.[1] Individuals with EDS demonstrate defects in the body's connective tissues, manifesting as altered strength, elasticity, integrity, and healing properties of the tissues. The severity of the syndrome varies greatly depending upon the specific mutation. However each type demonstrates some degree of integumentary involvement and/or joint hypermobility/laxity.[2]

Ehlers Danlos Syndrome traces its initial discover date and description to the fourth century BC. The first clinical description of EDS is credited to Tschernogobow in 1892. However, the name and recognition of the syndrome is credited to Edward Ehlers, a Danish dermatologist, and Henri-Alexandre Danlos, a French physician, both of who wrote separate reports in 1901 and 1908 respectively. The two physicians were able to collaborate in providing a description of the pertinent features of the condition as well as accurately identify the associated phenotypes.[2]

In 1997-1998, six discernable phenotypes for EDS were identified (classic, hypermobility, vascular, kyphoscoliosis, arthrochalasia, and dermatosparaxis) by Beighton et. al. These identifiable forms of EDS are currently recognized by the medical advisory board of the Ehlers-Danlos National Foundation and used in the clinical setting for proper diagnosis.[2] All of these phenotypes of EDS can lead to significant disability and decreased quality of life for the individual. The disability is multidimensional including physical impairments, chronic pain, fatigue, maladaptive cognition, and psychological stress.[3]

Prevalence

Combined prevalence of all subtypes of EDS is about 1 per 5,000. Hypermobility and classic subtypes are the most common with a prevalence of 1 per 10,000-15,000 and 1 per 20,000-40,000 respectively. EDS demonstrates equal prevalence amongst males and females of all racial and ethnic backgrounds. [2][4][5][6][7]

There are other forms of EDS that are very rare. These include the arthrochalasia, kyphoscoliosis, dermatosparaxis, and vascular types. Currently, only 30 cases of the arthrochalasia and 60 cases of kyphoscoliosis have been reported worldwide. The only cases of dermatosparaxis type have been seen in infants and children, and has only been found in a dozen individuals. The vascular type is the rarest form, affecting about 1 in 250,000 people worldwide. [8]

Characteristics/Clinical Presentation

Ehlers-Danlos Syndrome contains at least six discernible phenotypes that are individually recognized. However, each type contains characteristics similar to the others, often proving problematic in accurate diagnosis. Despite the frequent overlap of associated signs and symptoms of the various subtypes of EDS, each specific type presents with the same general clinical characteristics that are a result of faulty or reduced amounts of Type III collagen in the body:[2][5][4][6][7][9]

In 1997-1998, Beighton et al. in collaboration with the Ehlers-Danlos National Foundation proposed a system to distinguish the clinical manifestations of EDS into six distinct subtypes. This nosology is still being used in the clinical setting to achieve accurate diagnosis of EDS.[2][4][5][6][7][12]

Ultrastructural examination of collagen fibrils has been utilized as an assistive tool for diagnosis of Type I/II (Classical) EDS and Type VIIA/Type VIIB ( Arthrochalasia) EDS.[2][4]

Skin Biopsy using histopathologic analysis has yet to be proven as beneficial in the diagnostic process of EDS.[2][4]

Causes

EDS is classified as an inherited connective tissue disease. These patients’ tissues have greater amount of procollagen than normal and have a defect in the conversion of procollagen to collagen.[13] Three patterns of inheritance have been linked with the various subtypes of EDS: autosomal dominant, autosomal recessive, and X-linked (rarest form). The exact source of genetic mutation responsible for the condition is unknown. However, mutations in ADAMTS2, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, PLOD1, and TNXB genes have been linked to causation of EDS.[2][4]

COL1A1, COL1A2, COL3A1, COL5A1, COL5A2 encode the manufacture of proteins that are responsible for multiple types of collagen

ADAMTS2, PLOD1, and TNXB encode the manufacture of proteins that interact with or process collagen

Patients who have the vascular type EDS also lack type III collagen. Type III collagen is fibrillation forming collagen of 3 alpha-1 chains and is the most abundant type of collagen in the human body. In adults, it makes up the majority of the extracellular matrix in internal organs, especially the cardiovascular system and skin, resulting in arterial and vein complications. Sudden death has been reported in some cases.[14]

Generalized muscle weakness-- more likely due to a muscle dysfunction than atrophy and muscle loss

Decreased reflexes in the knee extensors and flexors seen in adolescents

Neurological

Fatigue, pain and anxiety are often due to exhaustion of the CNS's reserves

Migraines often disabling

Chronic pain results from the tight link of peripheral biomechanic dysfunctions and CNS fatigue. This often leads to fear of movement that is aggravated with activity, ultimately leading to muscular deconditioning.

Hyperalgesia is commonly seen in children and adults with hypermobility EDS due their central nervous system being highly sensitized

Aortic Root Dilation resulting in predisposition to arterial fragility or rupture. Typically occurs in a mild form in 25-33% of individuals with hypermobility and classic subtypes of EDS. Appears to be less severe than found in Marfan's Syndrome displaying no increased risk of dissection unless a prominent dilatation is present. Places individual at an increased risk for development of an abdominal aortic aneurysm (AAA).

Currenly Ehlers-Danlos Syndrome has no cure. Treatment and management of the condition includes a combination of prevention, management, and education about the specific characteristics of the syndrome as well as how to avoid primary and secondary manifestations of the condition. Presently a specific treatment protocol does not exist due to the large variability of signs and symptoms present in affected individuals and amongst the various subtypes of EDS. Each specific treatment protocol is individually designed and specialized for the affected individual in order to meet the needs of that specific patient.

Treatment of EDS typically consists of management of specific signs and symptoms of the condition as well as lifestyle adjustments to prevent injury/complications. Medical management is usually overseen by a physician specializing in physiatry/physical medicine and rehabilitation (PM&R). Referral sources include a physical therapist, occupational therapist, dentist, ophthalmologist, and genetic counselor to provide the patient with a comprehensive and holistic treatment approach.

A recent study on women with hypermobility type EDS showed significant improvement in performance, performance satisfaction, and decreased kinesiophobia when provided with an intensive multidisciplinary rehabilitation program. This included a cognitive-behavioral approach with strength and endurance training and pain coping.

Education

Avoidance of high impact activities that place increased stress on pre-morbid lax joints, such as heavy lifting or resistance training

Avoidance of activities that require joint hyperextension, such as excessive stretching or repetitive activities

Exercise program consisting of aerobic conditioning combined with a low resistance, high repetition resistive training program to promote increased joint stability by increasing general resting muscle tone

Consultation to screen for myopia, retinal tears, and keratoconus common in individuals with EDS

Dentist

Consultation to screen for periodontitis and to emphasize importance of meticulous dental care in individuals with EDS

Surgical/Invasive Procedures

Surgical and/or other invasive procedures are not necessarily recommended in patients with EDS as a means of primary treatment due to the impaired wound healing, increased likelihood of scarring, and increased likelihood of blood vessel rupture associated with EDS. However, certain subtypes of EDS, most notably the classic and vascular subtypes of EDS possess an increased predisposition to surgical complications compared to the others.

Arthroscopic debridement, tendon relocations, capsulorraphy, and arthroplasty have been performed on individuals with EDS with degree of stabilization, pain relief, patient satisfaction, and overall improvements being variable and less than individuals without EDS

Prolotherapy - A procedure, in which saline/other irritants are injected into tendons or surrounding joints to produce inflammation and subsequent scar formation in hopes of creating increased soft tissue stability

Anesthetic/corticosteroid injections - A procedure designed to address acute, localized areas of pain and inflammation by injecting anti-inflammatory solutions/medications

Anesthetic nerve blocks - A procedure, in which an injection occurs to specific nerve using anesthetic medication to provide temporary pain relief resulting from a neuropathic origin

Intrathecal anesthesia/opioid medication - A constant delivery of numbing/pain medication to address the presence of chronic pain and to reduce the need for oral/systemic medications

Unfortunately, no set protocol of physical therapy interventions exists to address the impairments and functional limitations associated with EDS, due largely in part to the varied presentation of the condition for each affected individual. Therefore, each physical therapy plan of care must be specially created for the patient depending upon the subtype of EDS and the signs and symptoms of that patient.

In general, physical therapy intervention focuses on decreasing the patient’s disability from a multidirectional approach. This includes ADLs, ambulation, sports activities, and quality of life. Functional activities and therapeutic exercises will be aimed at increasing joint stability through proprioceptive training, gentle stretching, resistance training and use of adaptive equipment to accomplish ADLs. It will be crucial to monitor vitals throughout treatment, especially blood pressure, in this population. This is particularly important in the subtypes that involve the cardiovascular system.

A recent systematic review presented the evidence-based rationale for physical therapy treatment of children, adolescents, and adults diagnosed with joint hypermobility syndrome/hypermobile Ehlers Danlos syndrome. Simmonds et al. conclude that PT's "play an important role in management through exercise prescription and patient education for many of these conditions". However, more robust high quality research needs to be performed in this patient population for assessment of conservative and surgical management[20].

Outcome MeasuresThere is currently not adequate research for specific EDS outcomes. However, these are some of the suggested assessment tools used to measure progress of impairments in this population. It is possible many different measurements could be used that focus on balance, gait speed, cadence, dual-task activities, quality of life, and fear of falling.

Goal is to reduce the presence of muscle spasms that result in intense pain in muscles and surrounding ligaments, tendon, and joints

Modalities

Hot/cold pack

Massage

Ultrasound

Electrical stimulation

Acupuncture

Acupressure

Goal is to provide pain relief to the patient, who may/may not be experiencing chronic muscle and joint pain from frequent joint subluxations/dislocations, myofascial spasms, and trigger points associated with EDS

Selection of proper modality is dependent upon patient preference

Adaptive Equipment

Wheelchair/scooter

Walker/Crutches/Cane (should be used with caution and discretion due to increased weight bearing through upper extremities with use)

Goal is to allow daily functioning and promote increased quality of life by decreasing pain or chance of joint subluxation/dislocation

According to Woinarosky “the reported prevalence of JHS/hEDS in adult physical therapy outpatient musculoskeletal settings has been reported to be between 30% and 55%."[10] Despite diagnostic differences between Hypermobility Syndrome and genetic disorders (characterized by generalized joint hypermobility), such as Ehlers-Danlos Syndrome, similar treatment approaches and interventions remain relevant and appropriate between the two diagnostic categories. Russek advocates the use of education and exercise as potential interventions for Hypermobility Syndrome. Education on ergonomics and body mechanics may result in decreases in musculoskeletal pain as well as assist in joint protection strategies. Splints, braces, and taping may also function as viable options to protect vulnerable joints. Russek suggests that therapeutic exercises, such as strengthening, proprioceptive activities, balance, and coordination to affected and surrounding joints as a means for treatment of Hypermobility Syndrome.[21][22]

Characterized by additional skeletal, ocular, cardiovascular, pulmonary, and integumentary signs and symptoms beyond those characteristic of EDS. Mimics hypermobility subtype of EDS, but clinical diagnosis is confirmed by the presence of a mutation in the FBN1 gene.

Loeys-Dietz Syndrome

Characterized by multiple arterial aneurysms and tortuosity. Other clinical signs and symptoms include ocular hypertelorisma and a bifid uvula. Mimics vascular subtype of EDS, but clinical diagnosis is confirmed by detection of a mutation in the TGFBR1 or TGFBR2 gene.

Stickler Syndrome

Characterized by sensorineural hearing loss, vitreoretinal abnormalities, and cleft palate. Clinical diagnosis is often based on the presence of clinical features, but the syndrome has been associated with mutations in one of three genes (COL2A1, COL11A1, or COL11A2)

Characterized by a shawl scrotum, widow's peak, short upturned nose, other dysmorphic features, and occasionally mental retardation. Clinical diagnosis consists of presence of a mutation of the FGD1 gene.

Fragile X Syndrome

Not commonly confused with EDS, but does share some characteristics similar to EDS such as joint laxity and EDS-like skin abnormalities. In affected males, characterized by large head, long face, prominent forehead and chin, protruding ears, joint laxity, large testes, and moderate retardation. In affected females, characterized by mild retardation. Clinical diagnosis consists of the presence of a mutation of the FMR1 gene.

Achondroplasia/hypochondroplasia

Characterized by short stature with distinguished skeletal features. Clinical diagnosis consists of characteristic clinical and radiographic findings in 70-99% of affected individuals as well as the presence of a mutation in the FGFR3 gene.

Characterized by the presence of multiple fractures and in some cases, dentinogenesis imperfecta (grey or brown teeth). Biochemical testing reveals the presence of abnormalities in structure and quantity of type I collagen (98% of type II OI, 90% of type I OI, 84% of type IV OI, 84% of type III OI). About 90% of individuals with Type I-IV OI present with a mutation in either the COL1A1 or COL1A2 genes.

Aneuploidies (Down Syndrome, Turner Syndrome, Klinefelter Syndrome)

Characterized by easily recognizable dysmorphic features and/or mental retardation with severity dependent upon degree of chromosomal deletions or duplications.

The content on or accessible through Physiopedia is for informational purposes only. Physiopedia is not a substitute for professional advice or expert medical services from a qualified healthcare provider. Read more